Clusterization in head and neck squamous carcinomas based on lncRNA expression: molecular and clinical correlates.

Clusterization in head and neck squamous carcinomas based on lncRNA expression: molecular and clinical correlates.
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DOI:
10.1186/s13148-017-0334-6
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发表时间:
2017
影响因子:
5.7
通讯作者:
García-Escudero R
García-Escudero R
中科院分区:
医学1区
文献类型:
--
作者:
de Lena PG;Paz-Gallardo A;Paramio JM;García-Escudero R

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长链非编码RNA(lncRNA)已经成为包括癌症在内的各种生物过程和病理条件中的关键参与者。下一代测序技术和生物信息学程序预测了数万种lncRNA的存在,从中我们只知道其中少数几种的功能,而对头颈部鳞状细胞癌(HNSCC)等癌症类型知之甚少。在这里,我们使用来自癌症基因组图谱(TCGA)的RNAseq表达数据和各种统计和软件工具,以了解HNSCC中的lncRNome。基于426个样本中的lncRNA表达,我们发现了五个不同的肿瘤簇,并与基于各种基因组/遗传特征的报告簇进行了比较。结果表明基于lncRNA的聚类与DNA甲基化、TP 53突变和人乳头瘤病毒感染之间存在显著相关性。使用“内疚协会”的程序,我们推断每个集群的代表性lncRNA的可能的生物学功能。此外,我们发现lncRNA聚类与一些重要的临床和病理特征相关,包括治疗后患者的生存率、肿瘤分级或亚解剖位置。我们提出了一个景观lncRNA在HNSCC和提供协会与重要的基因型和表型特征,可能有助于了解疾病。本文的在线版本(doi:10.1186/s13148-017-0334-6)包含补充材料,可供授权用户使用。
Long non-coding RNAs (lncRNAs) have emerged as key players in a remarkably variety of biological processes and pathologic conditions, including cancer. Next-generation sequencing technologies and bioinformatics procedures predict the existence of tens of thousands of lncRNAs, from which we know the functions of only a handful of them, and very little is known in cancer types such as head and neck squamous cell carcinomas (HNSCCs). Here, we use RNAseq expression data from The Cancer Genome Atlas (TCGA) and various statistic and software tools in order to get insight about the lncRNome in HNSCC. Based on lncRNA expression across 426 samples, we discover five distinct tumor clusters that we compare with reported clusters based on various genomic/genetic features. Results demonstrate significant associations between lncRNA-based clustering and DNA methylation, TP53 mutation, and human papillomavirus infection. Using “guilt-by-association” procedures, we infer the possible biological functions of representative lncRNAs of each cluster. Furthermore, we found that lncRNA clustering is correlated with some important clinical and pathologic features, including patient survival after treatment, tumor grade, or sub-anatomical location. We present a landscape of lncRNAs in HNSCC and provide associations with important genotypic and phenotypic features that may help to understand the disease. The online version of this article (doi:10.1186/s13148-017-0334-6) contains supplementary material, which is available to authorized users.